Leprosy is a chronic infectious disease prevalent in underdeveloped countries. There are thought to be 15 million cases worldwide of which 5 million are confirmed. Leprosy presents many immunological problems, but 3 major ones have been identified by WHO. 1. The diagnosis of leprosy using immunological methods. 2. The development of a prophylactic vaccine, and 3. Elucidation of the immunological factors which underly various complications of leprosy, including peripheral neuropathy and anergy. We have developed a research program that is addressed to the first and third of these problems. Projects 1 and 2 are concerned with diagnosis of leprosy. The first project seeks to identify in the urine of leprosy patients both mycobacterial antigens and host products that are generated in response to leprosy infection. It is hoped to develop a simple urine test for leprosy that would be applicable to large scale diagnostic and epidemiologic studies. The second project is concerned with the use of delayed hypersensitivity skin (DTH) reactions in leprosy. The kinetics and immunocytochemistry of DTH reactions to soluble M. leprae antigens will be studied to discover the potential diagnostic value of such tests, their prognostic significance, and the immunological mechanisms that determine the type of DTH reaction. Project 3 is based on the hypothesis that some of the manifestations of leprosy neuropathy are mediated by autoimmune mechanisms. To this end immunocytochemistry will be used to study binding of suspected autoantibodies to diseased and normal nerves; and to measure nerve-antigen-specific antibodies in the serum. Project 4 seeks to uncover the presence of M. leprae-reactive T cells in anergic patients by the application of limiting dilution and T cell cloning techniques.